SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys.
BACKGROUND
Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide.


RESULTS
We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis.


CONCLUSIONS
These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.
Humbert
Michael
M
Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. michael_humbert@dfci.harvard.edu
Rasmussen
Robert A
RA
Song
Ruijiang
R
Ong
Helena
H
Sharma
Prachi
P
Chenine
Agnès L
AL
Kramer
Victor G
VG
Siddappa
Nagadenahalli B
NB
Xu
Weidong
W
Else
James G
JG
Novembre
Francis J
FJ
Strobert
Elizabeth
E
O'Neil
Shawn P
SP
Ruprecht
Ruth M
RM
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D012692:Serial Passage; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
D014759:Viral Envelope Proteins